• Repurposed drugs present new strategy fo

    From ScienceDaily@1:317/3 to All on Thu Jul 8 21:30:34 2021
    Repurposed drugs present new strategy for treating COVID-19
    Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates

    Date:
    July 8, 2021
    Source:
    The Korea Advanced Institute of Science and Technology (KAIST)
    Summary:
    Researchers have identified repurposed drugs for COVID-19
    treatment through virtual screening and cell-based assays. The team
    suggested the strategy for virtual screening with greatly reduced
    false positives by incorporating pre-docking filtering based on
    shape similarity and post- docking filtering based on interaction
    similarity. This strategy will help develop therapeutic medications
    for COVID-19 and other antiviral diseases more rapidly.



    FULL STORY ==========================================================================
    A joint research group from KAIST and Institut Pasteur Korea has
    identified repurposed drugs for COVID-19 treatment through virtual
    screening and cell- based assays. The research team suggested the
    strategy for virtual screening with greatly reduced false positives
    by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will
    help develop therapeutic medications for COVID- 19 and other antiviral
    diseases more rapidly. This study was reported at the Proceedings of
    the National Academy of Sciences of the United States of America (PNAS).


    ========================================================================== Researchers screened 6,218 drugs from a collection of FDA-approved drugs
    or those under clinical trial and identified 38 potential repurposed
    drugs for COVID-19 with this strategy. Among them, seven compounds
    inhibited SARS-CoV- 2 replication in Vero cells. Three of these drugs,
    emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in
    human lung cells, Calu-3.

    Drug repurposing is a practical strategy for developing antiviral drugs
    in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most
    of the predicted drug candidates are false positives.

    The research group developed effective filtering algorithms before
    and after the docking simulations to improve the hit rates. In the
    pre-docking filtering process, compounds with similar shapes to the
    known active compounds for each target protein were selected and used
    for docking simulations. In the post- docking filtering process, the
    chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds.

    The experimental results showed that the virtual screening strategy
    reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected.

    "We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn't resolve the toxicity issues in preclinical trials," said Woo Dae Jang, one of the researchers
    from KAIST.

    "The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19
    treatment. If we use this technology, we will be able to quickly respond
    to new infectious diseases as well as variants of the coronavirus,"
    said Distinguished Professor Sang Yup Lee.

    This work was supported by the KAIST Mobile Clinic Module Project funded
    by the Ministry of Science and ICT (MSIT) and the National Research
    Foundation of Korea (NRF). The National Culture Collection for Pathogens
    in Korea provided the SARS-CoV-2 (NCCP43326).

    ========================================================================== Story Source: Materials provided by The_Korea_Advanced_Institute_of_Science_and_Technology_ (KAIST). Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Woo Dae Jang, Sangeun Jeon, Seungtaek Kim, Sang Yup Lee. Drugs
    repurposed
    for COVID-19 by virtual screening of 6,218 drugs and cell-based
    assay.

    Proceedings of the National Academy of Sciences, 2021; 118 (30):
    e2024302118 DOI: 10.1073/pnas.2024302118 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2021/07/210708103611.htm

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